Peanut allergy (PA) is a severe form of food allergy for which Improved treatments are needed. However, few Studies have been conducted to optimize the safety of oral immunotherapy (OIT) for PA, to tailor OIT protocols according to the needs of individual PA patients, or to identify the immunological mechanism(s) underlying any long-lasting effects of oral immunotherapy (OIT) in such subjects. Specifically, It is not yet clear what factors will determine, in individual subjects, whether OIT induces tolerance (in which no set dally use of that food alleroen is needed to allow for its safe consumption). To address these challenges, the Stanford Alliance for Food Allergy Research (SAFAR) plans to link the findings of the Phase 2 clinical study proposed here in Project 1 with the results of each of the other 3 projects of the U19 proposal focused on mechanistic studies (Projects 2, 3 & 4), as well as with the results ofthe immune metrics assays carried out by Scientific Core B. Each of these projects and Core B will use patient samples from Project 1 collected at screening and longitudinally throughout the clinical study to Integrate all data. We propose 3 main goals of our research for Project 1: Specific Aim 1: Test whether treatment of PA patients with OIT allows tolerance to be achieved (i.e., allows the subject to stop maintenance ingestion of peanut [during an avoidance period] for 3 months or more but then still undergo a successful double-blind placebo-controlled food challenge [DBPCFC] with peanut). Specific Aim 2: Determine whether treatment with our OIT protocol is safe in children and adults with peanut allergy (PA). Specific Aim 3: Evaluate to what degree current laboratory and clinical testing methods are associated with safety and tolerance outcomes (as identified in Specific Aims 1 and 2) in subjects with PA. By pursuing these aims, we will both: 1) provide the clinical samples, and the clinical outcome data, that will permit the innovative immune monitoring and mechanistic studies proposed in this U19 application to be accomplished, and 2) determine whether performing such immune monitoring has the potential to permit Individualization and optimization of safe and efficacious OIT protocols for individual PA patients.